Project summary The key benefit of our virtual neuroprosthetic framework proposed in the parent R01 grant (1R01EB025819) is that multiple hypotheses can be tested simultaneously using dorsal root ganglia (DRG) cultures in a cost- effective manner. The overall goal of this supplement grant is to augment the haptic signaling pathways that are restored in the virtual neuroprosthetic platform from one to four, consistent with human anatomy. Compared to the parent R01 in which we proposed to model only one pathway for a type of slowly adapting mechanoreceptor in the fingertip (continuously signaling the grasp force applied by the robotic hand), we propose herein to explore multiple parallel channels to mimic the complex functional anatomy of the hand which contains at least four different sensory receptor types carrying information on different aspects of the haptic experience (pressure, vibrational information used to detect slippage, texture, hand conformation, etc). These signals provide important complementary haptic information for the fine control of movements. Therefore, neurostimulation of DRG cultures mimicking the signals from different mechanoreceptors will produce distinctive spatial, temporal and functional forms of DRG regeneration post-axotomy, and the resulting functional diversity of regenerated pathways will ultimately play a key role in the overall quality of somatosensory restoration after amputation, supporting better usage of haptic feedback-enabled hand protheses. Specifically, we propose to (1) design highly realistic electrical stimulation patterns from the four principal types of slowly adapting (SA) and rapidly adapting (RA) mechanoreceptors to electrically stimulate DRGs cultured in microfluidic chambers, (2) to study the contribution of those multiple pathways, individually and synergistically, to anatomical and functional restoration, and (3) to establish if this restoration scheme surpasses one with the lower attentional load but lesser informational richness obtained when the haptic feedback is derived from only one functional pathway, as is currently under investigation within the parent R01.